Pregabalin versus Gabapentin

How does pregabalin compare to gabapentin in the treatment of neuropathic pain?

David F. McAuley, Pharm.D.
GlobalRPh Inc.

Pregabalin versus gabapentin:
Pregabalin, like gabapentin, is an amino acid derivative of gamma-amino butyric acid (GABA
analogue).1,2 Pregabalin is the pharmacologically active S-enantiomer of 3-aminomethyl-5-methyl-hexanoic acid, and has a similar pharmacological profile to
gabapentin.1 These agents are part of a unique class that have a high affinity to the alpha-2-delta protein in the
CNS.3,4,5 Both agents have been shown to be effective for neuropathic pain disorders, however, only prebabalin has been FDA approved for both the management of diabetic peripheral neuropathy and post herpetic
neuralgia.3,6,7

Pregabalin has been shown in studies to provide equivalent efficacy to gabapentin, however, at much lower
doses.3,5 Because lower dosages can be used to treat neuropathic pain, it is likely that pregabalin will be associated with fewer dose-related adverse
events.3,5 Part of the reason why pregabalin requires lower dosages is that it has a much higher bioavailability (90% versus 33-66%) and is rapidly absorbed (peak: 1 hr). Also, plasma concentrations increase linearly with increasing
dose.3 This is not true with gabapentin. Gabapentin is slowly absorbed (peak: 3 to 4 hours post-dose) and more importantly, plasma concentrations have been found to have a non-linear relationship to increasing doses. Pregabalin has been found to have distinct pharmacokinetic advantages over
gabapentin.3

Pregabalin has shown greater potency than gabapentin in pain and seizure
disorders.6 J. Fehrenbacher et al stated that pregabalin has been shown to have greater analgesic activity in rodent models of neuropathic
pain.2 Further, D. Wesche et al noted that pregabalin is approximately 2.5 times more potent than gabapentin based on plasma
concentrations.3

M. Vera-Llonch et al estimated analgesic outcomes in patients with painful diabetic peripheral neuropathy or post-herpetic neuralgia receiving pregabalin versus gabapentin.8 They developed a model to estimate the impact on analgesic outcomes of treatment with pregabalin (375 mg/day) versus gabapentin (1200 mg/day and 1800 mg/day) in a hypothetical cohort of 1,000 patients with diabetic peripheral neuropathy or post-herpetic neurolgia. Targeted outcomes included the mean number of days with no or mild pain (score<3), and days with at least a thirty to fifty percent reduction in pain intensity. The study concluded that pregabalin may provide better analgesic outcomes than gabapentin over a 12-week period.

Conclusion:
Further head-to-head trials are needed to provide further evidence supporting the use of pregabalin over gabapentin in the treatment of neuropathic pain. Current study results appear to provide early support for pregabalin based on its greater potency and pharmacokinetic superiority. Pregabalin is generally well tolerated with the most common adverse effects reported being dizziness, somnolence and peripheral
edema.1